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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules and Therapeutics
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The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 16, Issue 4 - Dec 2008
Volume 16, Issue 3 - Sep 2008
Volume 16, Issue 2 - Jun 2008
Volume 16, Issue 1 - Mar 2008
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Serum Deprivation Enhances Apoptotic Cell Death by Increasing Mitochondrial Enzyme Activity
Moon, Eun-Yi ;
Biomolecules and Therapeutics, volume 16, issue 1, 2008, Pages 1~8
DOI : 10.4062/biomolther.2008.16.1.001
Mitochondria are important sensor of apoptosis.
cell death rate was enhanced by serum deprivation. In this study, we investigated whether serum deprivation using 0.5 or 3 % FBS induces apoptotic cell death through mitochondrial enzyme activation as compared to 10 % FBS. Apoptotic cell death was observed by chromosome condensation and the increase of sub-G0/G1 population. Serum deprivation reduced cell growth rate, which was confirmed by the decrease of S-phase population in cell cycle. Serum deprivation significantly increased caspase-9 activity and cytochrome c release from mitochondria into cytosol. Serum deprivation-induced mitochondrial changes were also indicated by the increase of ROS production and the activation of mitochondrial enzyme, succinate dehydrogenase. Mitochondrial enzyme activity increased by serum deprivation was reduced by the treatment with rotenone, mitochondrial electron transport inhibitor. In conclusion, serum deprivation induced mitochondrial apoptotic cell death through the elevation of mitochondrial changes such as ROS production, cytochrome c release and caspase-9 activation. It suggests that drug sensitivity could be enhanced by the increase of mitochondrial enzyme activity in serum-deprived condition.
Antioxidant and Anti-Nociceptive Activities of Ulmus davidiana var. japonica
Jung, Hyun-Joo ; Kang, Hyun-Jung ; Song, Yun-Seon ; Lim, Chang-Jin ; Park, Eun-Hee ;
Biomolecules and Therapeutics, volume 16, issue 1, 2008, Pages 9~13
DOI : 10.4062/biomolther.2008.16.1.009
Some pharmacological activities of Ulmus davidiana var. japonica were evaluated using its methanol extract (UDE). An acute anti-inflammatory activity of UDE was assessed using carrageenan-induced hind paw edema in rats. UDE exhibited an antioxidant activity when assayed by a stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). Dose-dependent anti-nociceptive activity of UDE was assessed using the acetic acid-induced writhing test in mice. UDE was able to diminish the reactive oxygen species (ROS) level in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. UDE also suppressed production of nitric oxide and induction of inducible nitric oxide synthase and cyclooxygenase-2 in the stimulated macrophages cells. collectively, the results imply that U. davidiana var. japonica has antioxidant and anti-nociceptive activities in addition to anti-inflammatory activity.
Regulation of Choline Transport by Oxidative Stress at the Blood-Brain Barrier In Vitro Model
Kang, Young-Sook ; Lee, Hyun-Ae ; Lee, Na-Young ;
Biomolecules and Therapeutics, volume 16, issue 1, 2008, Pages 14~20
DOI : 10.4062/biomolther.2008.16.1.014
In the present study, we examined how the transport of choline is regulated at the blood-brain barrier (BBB) under the central nervous system (CNS) cellular damages by oxidative stress using a conditionally immortalized rat brain capillary endothelial cells (TR-BBB), in vitro the BBB model. It was also tested whether the choline uptake is influenced by membrane potential, extracellular pH, protonophore (FCCP) and amiloride in TR-BBB cells. In result,
uptake was inhibited by FCCP and dependent on extracellular pH. The treatment of TR-BBB cells with 20 ng/mL tumor necrosis
, 10 ng/mL lipopolysaccharide (LPS), 100
diethyl maleate (DEM) and 100
glutamate resulted in 3.0-fold, 2.6-fold, 1.8-fold and 2.0-fold increases of
uptake at the respective peak time, respectively. In contrast, hydrogen peroxide and raffinose did not show any significant effects on choline uptake. In addition, choline efflux was significantly inhibited by
, LPS and DEM producing cell damage states. In conclusion, the influx and efflux transport system for choline existed in TR-BBB cell line and this process was affected by several oxidative stress inducing agents.
Role of Intracellular Calcium in Clotrimazole-Induced Alteration of Cell Cycle Inhibitors, p53 and p27, in HT29 Human Colon Adenocarcinoma Cells
Thapa, Dinesh ; Kwon, Jun-Bum ; Kim, Jung-Ae ;
Biomolecules and Therapeutics, volume 16, issue 1, 2008, Pages 21~27
DOI : 10.4062/biomolther.2008.16.1.021
Clotrimazole (CLT), a potent antifungal drug, is known to inhibit tumor cell proliferation. In the present study, we examined the role of intracellular
in CLT-induced cell cycle arrest of colon adenocarcinoma HT29 cells. CLT inhibited growth of HT29 cells in a concentration-dependent manner, which was associated with inhibition of cell cycle progression at the G(1)-S phase transition and an increase in the expression of cell cycle inhibitor proteins p27 and p53. CLT also suppressed the
overload by A23187, a calcium ionophore, suggesting its role in modulation of intracellular
concentration in HT29 cells. The simultaneous application of CLT and A23187 with addition of
(1mM) to the medium significantly reversed CLT-induced p27 and p53 protein level increase and growth suppression. Our results suggest that CLT induces cell cycle arrest of colon adenocarcinoma HT29 cells via induction of p27 and p53, which may, at least in part, be mediated by alteration of intracellular
An Efficient Method for the Large-Scale Synthesis of Atorvastatin Calcium
Lee, Hong-Woo ; Kim, Young-Min ; Yoo, Choong-Leol ; Kang, Sung-Kwon ; Ahn, Soon-Kil ;
Biomolecules and Therapeutics, volume 16, issue 1, 2008, Pages 28~33
DOI : 10.4062/biomolther.2008.16.1.028
Atorvastatin calcium salt (1) was obtained through the preparation of lactone compound (8) from 2-((4R,6R)-6-(2-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-ethyl)-2-phenyl-1,3,2-dioxaborinan-4-yl)acetic acid tert-butyl ester (9) by hydrolysis in basic condition. Efficient hydrolysis of boronate compound 9 aimed at the viable synthesis for commercial production and purification of Atorvastatin calcium is reported. Detail studies of evaluation procedure are also reported.
Activity Change of Sphingomyelin Catabolic Enzymes during Dimethylnitrosamine-induced Hepatic Fibrosis in Rats
Sacket, Santosh J. ; Im, Dong-Soon ;
Biomolecules and Therapeutics, volume 16, issue 1, 2008, Pages 34~39
DOI : 10.4062/biomolther.2008.16.1.034
Oxidative stress may represent a common link between chronic liver damage and hepatic fibrosis. In the present study, we investigated activity changes of sphingomyelin catabolic enzymes, such as sphingomyelinases and ceramidases by using dimethylnitrosamine (DMN)-treated Sprague-Dawley (SD) male rats hepatic fibrosis model as a hepatic fibrosis model. Twenty rats divided into five groups received: (1) saline; (2) DMN for 1 week, (3) DMN for 2 weeks, (4) DMN for 3 weeks, and (5) DMN for 4 weeks by intraperitoneally 10 mg/kg of body weight for three consecutive days a week. Activities of acidic and neutral sphingomyelinases and acidic, neutral and alkaline ceramidases were measured in the liver and kidney from DMN-treated rats. We found increased ceramidase activities from 2-week and/or 3-week DMN treated rat livers compared to control rat liver. Acidic sphingomyelinase and alkaline ceramidase activities were significantly increased in 3-week DMN-treated rat kidneys compared to control rat kidney. Therefore, sphingolipid metabolizing enzymes and sphingolipid metabolites are supposed to be involved in liver fibrosis, although further investigation is necessary to elucidate meanings of sphingolipids during the liver fibrosis
Toxicity of Aceporol 330 in Mice as Novel Solubilizer of Paclitaxel
Kim, Yeo-Woon ; Chung, Kyu-Nung ; Kang, Hoon-Suk ; Sheen, Yhun-Yhong ;
Biomolecules and Therapeutics, volume 16, issue 1, 2008, Pages 40~45
DOI : 10.4062/biomolther.2008.16.1.040
The objective of this study was to investigate the single dose and 2-week repeated dose toxicity of Aceporol 330 in ICR mice following single intravenous administration and to compare its toxicity with a commercially available solubilizer of paclitaxel, Cremophor EL. In single dose toxicity test,
of Aceporol 330 in mice was estimated to be greater than maximum applicable dose, 4 ml/kg. However,
of Cremophor EL in male mice was determined to be 4 ml/kg. Maximum tolerated dose (MTD) of males and females in Aceporol 330-treated group and MTD of females in Cremophor EL-treated group were 3 ml/kg. MTD of males in Cremophor EL-treated group was less than 3 ml/kg. Characteristic toxic symptoms, and hematological and blood chemical changes were not observed after single dose and repeated dose of Aceporol 330 or Cremophor EL. No histopathological abnormalities were found in organs of all animal groups. Based on the linear pharmacokinetic property of paclitaxel and the higher
in mice, Aceporol 330 has a potential for use as a safer solubilizer for paclitaxel than Cremophor EL.
Hypolipidemic and Hepatoprotecitive Effects of Picrorrhiza Rhizoma in High Fat Diet Supplied Mice. A Pevention Sudy.
Lee, Hyeung-Sik ; Woo, Sung-Jung ; Ku, Sae-Kwang ;
Biomolecules and Therapeutics, volume 16, issue 1, 2008, Pages 46~53
DOI : 10.4062/biomolther.2008.16.1.046
The preventive hypolipidemic effect of the aqueous extracts of Picrorrhiza Rhizoma (PR) was observed in a high fat diet (HFD) feeding hyperlipidemic mouse with their hepatoprotective effects. PR extracts (50, 100 and 200mg/kg) were orally dosed once a day for 12 weeks initiated with HFD supply, and changes on body weight and gains, liver weight, serum aspartate transferase (AST) and alanine transferase (ALT) levels were monitored with serum low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride and total cholesterol levels. The efficacy of test articles was compared to that of 10mg/kg of simvastatin (SIMVA). Dramatic decrease of both absolute and relative liver weight was dose-dependently observed in all PR extract dosing groups as compared with HFD control group. The serum AST and ALT levels were dose-dependently decreased in PR extract dosing groups. The serum LDL, triglyceride and total cholesterol levels were dose-dependently decreased in PR extract dosing groups compared to that of HFD control group. The serum HDL levels were slightly but dose-dependently increased in PR extract dosing groups as compared with control group. The efficacy on the serum lipid levels of PR extracts was slighter than that of SIMVA. Based on these results, it is concluded that water extract of PR has a relatively good favorable preventive effects on the HFD inducing hyperlipidemia and hepatopathy.
Comparative Drug Evaluation of Atorvastatin versus Rosuvastatin in Pharmacotherapy of Korean Patients with Dyslipidemia
Park, Seon-Young ; Lee, Myung-Koo ; Lim, Sung-Cil ;
Biomolecules and Therapeutics, volume 16, issue 1, 2008, Pages 54~60
DOI : 10.4062/biomolther.2008.16.1.054
Dyslipidemia is the multiple lipid metabolic disorders which is one of the high risk factors for the atherosclerotic diseases. It increases the morbidity and mortality and therefore, must be treated with antilipidemic agents. HMG-Co A reductase inhibitors (statins), one of many antidyslipidemic agents, have shown to be significant improvement from the various cholesterol levels. Especially, data from many comparative trials suggest that rosuvastatin is more effective than atorvastatin among many other statins. The aims of this study were to evaluate the efficacy and safety between rosuvastatin and atorvastatin in the treatment of Korean patients with dyslipidemia. Currently the Korean Society of Lipidology and Atherosclerosis based on the Korean health screening data suggests that Korean patients with dyslipidemia should be treated by the target cholesterol levels according to the Adult Treatment Panel III guidelines of the US National Cholesterol Education Program (NCEP-ATP III). We reviewed retrospectively all medical histories of the total 392 dyslipidemic patients with atorvastatin or rosuvastatin from June 1st, 2004 to August 31st, 2006 in Chungbuk National University Medical Center. Patients were classified as total 4 groups by the NCEP-ATP III Guidelines. The numbers of enrolled patients were each 5 mg atorvastatin (n=34), 10 mg atorvastatin (n=148), 5 mg rosuvastatin (n=94) and 10 mg rosuvastatin (n=82). In comparison between groups, rosuvastatin groups in the lowering LDL-C had better efficacies, and the results were each 22% (5 mg atorvastatin), 33.3% (10 mg atorvastatin), 35% (5 mg rosuvastatin) and 41.3% (10 mg rosuvastatin) with the dose relationship (P=0.000). Rosuvastatin groups also have shown to be more significantly reducing Total Cholesterol levels compared to atorvastatin groups with the no dose relationship (P=0.000). In the lowering of non-HDL cholesteroles, rosuvastatin groups showed significantly better efficacies than atorvastatin with the dose-relationship (P=0.000). Each medication groups did not demonstrate the differences in the changing of HDL cholesterol and triglyceride levels (P=0.096, 0.309, respectively). In conclusion, rosuvastatin was better efficacious than atrovastatin in reducing LDL-C Total Chol, and Tg. Therefore, rosuvastatin is a good antilipidemic agents for Korean patients with dyslipidemia and it can use to minimize the morbidity and mortality related to the cardiovascular diseases in Korean.
Toxicity of Novel Solubilizer of Paclitaxel, Aceporol 330, in Beagle Dogs
Kim, Yeo-Woon ; Chung, Kyu-Nung ; Kang, Hoon-Suk ; Sheen, Yhun-Yhong ;
Biomolecules and Therapeutics, volume 16, issue 1, 2008, Pages 61~68
DOI : 10.4062/biomolther.2008.16.1.061
In order to develop an improved paclitaxel formulation vehicle, a micelle forming solubilizer, Aceporol 330 was synthesized. It was previously reported that Aceporol 330 provided the linearity of paclitaxel plasma pharmacokinetics. In this study, the single dose toxicity test and 2-week repeated dose toxicity test of Aceporol 330 was performed in beagle dogs after intravenous administration. Single dose and 2-week repeated dose toxicity test of Aceporol 330 showed fever/generalized erythema, severe vomiting, and diarrhea in beagle dogs. However, those toxicities were less severe than those of Cremophor EL. Blood chemistry analysis of 2-week repeatedly treated beagle dogs with Aceporol 330 showed significant elevation of total cholesterol (TCHO) and triglyceride (TG) compared to that of control group. Cremophor EL also significantly increased total cholesterol (TCHO) and triglyceride (TG) as much as Aceporol 330. Results from this study indicated that Aceporol 330 was less toxic than Cremophor EL. Based on the pharmacokinetic advantages and the low toxicity of Aceporol 330 in single dose and 2-week repeated dose toxicity test, Aceporol 330 has a potential for use as a safer solubilizer for paclitaxel than Cremophor EL.